Abstract
Phosphotyrosine phosphatase (PTPase) activity and its regulation by overnight food deprivation were studied in Psammomys obesus (sand rat), a gerbil model of insulin resistance and nutritionally induced diabetes mellitus. PTPase activity was measured using a phosphopeptide substrate containing a sequence identical to that of the major site of insulin receptor (IR) β-subunit autophosphorylation. The PTPase activity in membrane fractions was 3.5-, 8.3-, and 5.9-fold lower in liver, fat, and skeletal muscle, respectively, compared with corresponding tissues of albino rat.Western blotting of tissue membrane fractions in Psammomys showed lower PTPase and IR than in albino rats. The density of PTPase transmembrane protein band was 5.5-fold lower in liver and 12-fold lower in adipose tissue. Leukocyte antigen receptor (LAR) and IR were determined by specific immunoblotting and protein bands densitometry and were also found to be 6.3-fold lower in the liver and 22-fold lower in the adipose tissue in the hepatic membrane fractions. Liver cytosolic PTPase activity after an overnight food deprivation in the nondiabetic Psammomys rose 3.7-fold compared with postprandial PTPase activity, but it did not change significantly in diabetic fasted animals. Similar fasting-related changes were detected in the activity of PTPase derived from membrane fraction. In conclusion, the above data demonstrate that despite the insulin resistance, Psammomys is characterized by low level of PTPase activities in membrane and cytosolic fractions in all 3 major insulin responsive tissues, as well as in liver. PTPase activity does not rise in activity as a result of insulin resistance and nutritionally induced diabetes.
Highlights
Insulin resistance is an innate characteristic of the gerbil Psammomys obesus, known as sand rat [1,2,3]
Phosphotyrosine phosphatase (PTPase) activity and its regulation by overnight food deprivation were studied in Psammomys obesus, a gerbil model of insulin resistance and nutritionally induced diabetes mellitus
The obese humans demonstrated an increase in PTPase leukocyte antigen receptor (LAR) level in subcutaneous fat tissue where this enzyme was found responsible for the elevated total PTPase activity in the membrane fraction [14]
Summary
Insulin resistance is an innate characteristic of the gerbil Psammomys obesus, known as sand rat [1,2,3]. The resistance is caused by impaired transduction of the signal through the insulin receptor (IR) to the effector molecules in the cell, associated with overexpression of protein kinase C (PKC) isoenzymes in the skeletal muscle, of PKCε [3, 4]. It has been previously demonstrated that in Psammomys placed on high-energy diet, the activation of TK by insulin is impaired [4]. Appearance of high postprandial blood glucose levels is the hallmark for stage C in the course of the disease Such anomalous predisposition to diet-induced diabetes mellitus is characteristic for most of the Psammomys population, with the exception of a selectively inbred diabetesresistant line [21]. To investigate whether an increase in PTPase activity in Psammomys might contribute both to the innate insulin resistance and that induced by HE diet
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